ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.6654C>A (p.Asp2218Glu) (rs537236734)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000222742 SCV000271566 uncertain significance not specified 2015-02-26 criteria provided, single submitter clinical testing The p.Asp2218Glu variant in CDH23 has not been previously reported in individual s with hearing loss, but has been identified in 0.1% (9/8502) of East Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs537236734). Although this variant has been seen in the general popula tion, its frequency is not high enough to rule out a pathogenic role. Computatio nal prediction tools and conservation analysis suggest that this variant may imp act the protein, though this information is not predictive enough to determine p athogenicity. In summary, the clinical significance of the p.Asp2218Glu variant is uncertain.
GeneDx RCV000657978 SCV000779749 uncertain significance not provided 2018-04-02 criteria provided, single submitter clinical testing The D2218E variant in the CDH23 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D2218E variant is observed in 23/18860 (0.1%) alleles from individuals of East Asian background, in large population cohorts; however, no individuals were reported to be homozygous (Lek et al., 2016). The D2218E variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret D2218E as a variant of uncertain significance.

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